The Neurocritic

Thursday, October 30, 2014

In the mirror we see our physical selves as we truly are, even though the image might not live up to what we want, or what we once were. But we recognize the image as “self”. In rare instances, however, this reality breaks down.

In Black Swan, Natalie Portman plays Nina Sayers, a ballerina who auditions for the lead in Swan Lake. The role requires her to dance the part of the innocent White Swan (for which she is well-suited), as well as her evil twin the Black Swan — which is initially outside the scope of her personality and technical abilities. Another dancer is favored for the role of the Black Swan. Nina's drive to replace her rival, and her desire for perfection, lead to mental instability (and a breathtaking performance). In her hallucinations she has become the Black Swan.1

Perhaps Darren Aronofsky [the director's] intentions for the mirror was its power to reveal hidden identities. If you noticed the scenes where Nina saw herself in the mirror, it reflected the illusion of an evil. The mirror presented to her the darkness within herself that metaphorically depicted the evolution into the black swan.

How can the recognition of self in a mirror break down?

Alterations in mirror self-recognition

There are at least seven main routes to dissolution or distortion of self-image:

psychotic disorders

dementia

right parietal-ish or otherwise right posterior cortical strokes and lesions

Professor Max Coltheart and colleagues have published extensively on the phenomenon of mirrored-self misidentification, defined as “the delusional belief that one’s reflection in the mirror is a stranger.” They have induced this delusion experimentally by hypnotizing highly suggestible participants and planting the suggestion that they would see a stranger in the mirror (Barnier et al., 2011):

Following a hypnotic suggestion to see a stranger in the mirror, high hypnotizable subjects described seeing a stranger with physical characteristics different to their own. Whereas subjects' beliefs about seeing a stranger were clearly false, they had no difficulty generating sensible reasons to explain the stranger's presence. The authors tested the resilience of this belief with clinically inspired challenges. Although visual challenges (e.g., the hypnotist appearing in the mirror alongside the subject) were most likely to breach the delusion, some subjects maintained the delusion across all challenges.

Ad campaign for the Exelon Patch (rivastigmine, a cholinesterase inhibitor) used to treat Alzheimer's disease. Photographer Tom Hussey did a series of 10 award-winning portraits depicting Alzheimer's patients looking at their younger selves in a mirror (commissioned by Novartis).

Mendez et al. (1992) published a retrospective study of 217 patients with Alzheimer's disease. They searched the medical records for caregiver reports of disturbances in person identification of any kind. The most common type was transient confusion about family members that resolved when reminded of the person's identity (found in 33 patients). The charts of five patients contained reports of mirror misidentification, which was always associated with paranoia and delusions. Although not exactly systematic, this fits with other studies reporting that 2–10% of Alzheimer's patients have problems recognizing themselves in a mirror.

A thorough investigation of the topic was actually published 50 years ago, but largely neglected because it was in French. Connors and Coltheart (2011) translated the 1963 paper of Ajuriaguerra, Strejilevitch, & Tissot into English. The Introduction is quite eloquent:

The vision of our image in the mirror is a discovery that is perpetually renewed, one in which our being is isolated from the world, from the objects surrounding it, and assumes, despite the fixed quality of reflected images, the significance of multiple personal and potential expressions. The image reflected by the mirror furnishes us not only with that which is, but also how our real image might be changed. It therefore inextricably combines awareness, indulgence and critique.

They examined how 30 hospitalized dementia interacted with mirrors in terms of (1) recognition of their own reflection; (2) use of reflected space; and (3) identifying body parts. The patients sat in front of a mirror and answered the following questions:

What is this?

Who is that?

How old would you say that person is?

How do you think you look?

Then the experimenter stood behind them and asked questions about himself (e.g., “who is that man?”), and showed them objects in the mirror (e.g., an orange or a pipe – very funny).

Eight patients did not recognize themselves in the mirror:

Three didn't understand the concept of a mirror. They didn't pay attention to any reflections until directed to do so, and then they became transfixed. They also failed to recognize photos of themselves or their caretakers.

Another three eventually admitted it might be themselves when prodded several times.

Those six individuals had severe Alzheimer's disease.

The final two recognized themselves the second time, and displayed considerably more anxiety. This sounds terribly frightening:

These patients were attentive to their own reflections and those of the researchers, whom they identified. The first patient seemed a bit anxious; she began by touching herself, then laughed, then proclaimed “that is not quite me, it sort of looks like me, but it's not me.” When she was shown her photo head-on and then from the side, she immediately identified herself when the photo was head-on but from the side said “that's not quite me.”

These two individuals were in an earlier state of dissolution and likely had more awareness of what was happening to them.

Other patients with mirrored-self misidentification show greater sparing of cognitive abilities. Chandra and Issac (2014) presented brief case summaries of five mild to moderate dementia patients with “mirror image agnosia, a new observation involving failure to recognize reflected self-images.” This is obviously not a new observation, but the paper includes two videos, one of which is embedded below.

Sixty-two-year-old female was brought to the hospital with features of forgetfulness and getting lost in less familiar environment. ... She was then shown the mirror 45 cm × 45 cm. She could identify it as a mirror. She showed unusual attraction to the mirror and ignored the physician and people around. She would go to the mirror and converse with her own image as if the image is another person but could correctly identify the reflected face of her daughter in law and the resident but she was asking her own reflection for the name and communicated to others saying that ‘here is a woman who does not know her name’.

The participants reported that apparition of new faces in the mirror caused sensations of otherness when the new face appeared to be that of another, unknown person or strange `other' looking at him/her from within or beyond the mirror. All fifty participants experienced some form of this dissociative identity effect, at least for some apparition of strange faces and often reported strong emotional responses in these instances.

Saturday, October 25, 2014

Nightmares can seem very real at times, but then we wake up and realize it was all a bad dream. Now imagine having a vivid nightmare with all the reality of waking life and then... it turns out you're actually awake through it all!

This happened to an 11 year old Italian boy who reported frightening auditory and visual hallucinations of Voldemort, the archenemy of Harry Potter, for three straight days. These hallucinations began after a bout of sore throat and fever (38°C). As Vita et al. (2008) report:

The day after the resolution of fever, he began to present hallucinations. Hallucinations occurred in the afternoon, after watching TV. They were polymodal: he saw and heard Voldemort (an evil character of the Harry Potter saga). He did not realize his hallucinations were not real; he was extremely frightened, and he cried and searched his parents for protection. The episode lasted several hours, and was not associated with modification of vigilance or consciousness. ... Two days later, a new hallucinatory episode occurred: again, he saw Voldemort, who appeared threatening, and he fought against him. A further episode, with the same features, occurred the following day. He interacted with the characters of the hallucination, and on one occasion, he wore a sword and helmet to fight against Voldemort. When asked to recall the hallucinations, the boy said that they appeared real to him.

Neurological exam, EEG, and CSF cultures for bacteria, viruses, and fungi were all negative. CSF titers of antibodies were normal, and there was no evidence of autoantibodies. However, an MRI scan showed abnormal signs in the boy's brainstem. Several small lesions were observed in the pons, in the vicinity of a region implicated in REM sleep.

Fig. 1 (modified from Vita et al., 2008). MRI after the onset of hallucinations. Small areas of signal hyperintensity (lesions) are indicated by the arrows.

The etiology and phenomenology of the boy's condition seem consistent with peduncular hallucinosis, “a rare form of visual hallucination often described as vivid, colorful visions of people and animals.” The exact cause is unknown, but most cases have been related to lesions in the midbrain, thalamus, or brainstem (Dogan et al. 2013; Penney & Galarneau, 2014; Talih, 2013). In some instances the patients are aware that the hallucinations are not real, but other cases present as a psychiatric disorder and can include auditory or tactile hallucinations, in addition to visual.

Here, Vita et al. (2008) speculate that dreaming and REM sleep have become dissociated: the boy was literally dreaming while awake. Fortunately, his nightmarish condition disappeared after treatment with immunoglobulins. The exact diagnosis was unclear, but it might have been a transient demyelinating syndrome, which involves the loss of white matter, or myelin, that surrounds the axon.

The authors cited a model of REM sleep in which GABA-containing “REM-on” neurons inhibit GABAergic “REM-off” neurons located in the ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT), and vice versa.

Fig. 1 (modified from Vita et al., 2008). MRI after the onset of hallucinations. Three small lesions are indicated by the arrows.

Turns out the lesions (shown in gray stippling below) could include some of these neurons, especially those in the REM-off areas (vlPAG and LPT).

The authors speculated that transient dysfunction of REM-off cells, caused by the inflammatory demyelinating syndrome, resulted in weaker inhibition of REM-on cells, allowing a dream-like state to ooze into wakefulness.

Luckily the boy won out over Voldemort in the end, assisted by a team of doctors at Catholic University in Rome.

A group of researchers in Germany used text passages from the Harry Potter series to test the fiction feeling hypothesis, specifically that readers will experience a greater sense of empathy for and identification with the protagonists when the content is suspenseful and scary (Hsu et al., 2014). This would be accompanied by greater activations in specific brain regions during an fMRI scan.

The experimental stimuli were 80 passages from the Harry Potter novels. The authors selected 40 ‘fear-inducing’ and 40 ‘neutral’ passages, each about 4 lines long.1 These were screened and rated by a set of independent participants. Unfortunately, the authors did not provide any examples, so I'm going to have to improvise here.

Given that I've not read any of the Harry Potter books (or seen the movies), I'm not the best person to run a popular blog serial on NeuroReport's Harry Potter and the _______ books. Or to to launch an academic publishing franchise on fMRI studies of epic fantasy novels.2

He felt the unnatural cold begin to steal over the street. Light was sucked from the environment right up to the stars, which vanished. The cold was biting deeper and deeper into Harry’s flesh [and lighting up his pain matrix in an eerie glow against the dark and lonely night].

Then, around the corner, gliding noiselessly, came Dementors, ten or more of them, visible because they were of a denser darkness than their surroundings, with their black cloaks and their scabbed and rotting hands. Could they sense fear [and an overactive amygdala] in the vicinity? ...

My poorly written additions in maroon prefigure the focus of the study — empathy for pain. I'm not exactly sure why this was so (for either literary or scientific reasons). At any rate, Hsu et al. (2014) made the following predictions:

we expected (i) higher immersion ratings for fear-inducing passages, which often describe pain or personal distress, as compared with neutral passages, and (ii) significant correlations of immersion ratings with activity in the affective empathy network, particularly AI [anterior insula] and mCC [mid-cingulate cortex], associated with pain empathy for fear-inducing, but not for neutral, passages.

AI and mCC have been implicated in the affective component of personally felt pain, as well as in empathy for another person's pain (Jackson et al., 2006). So the expected result would be greater activations in AI and mCC for the Fearful vs. Neutral comparison. They didn't do this exact contrast, but they did look for differential correlations between “immersion ratings” and BOLD responses for Fear > fixation (a low-level control condition) and Neutral > fixation.

A separate group of individuals (not the ones who were scanned) rated the Fearful and Neutral passages for immersion by rating their subjective experience, ‘I forgot the world around me while reading’ on a scale from 1 (totally untrue) to 7 (totally true). Although the difference between Fear (mean = 3.75) and Neutral (mean = 3.18) was statistically significant, the level of immersion wasn't all that impressive, being below the midpoint even for the scary texts.

The major fMRI result was a cluster in the mid-cingulate cortex (corrected cluster-level P = 0.037) that showed a higher correlation between immersion ratings and BOLD for Fear than for Neutral.

No such relation was observed in the anterior insula, which was explained by postulating that “motor affective empathy” was more prominent than “sensory affective empathy”:

Craig [12] considered mCC to be the limbic motor cortex and the site of emotional behavioural initiation, whereas AI is the sensory counterpart. With respect to our stimuli from Harry Potter series, in which behavioural aspects of emotion are particularly vividly described, the motor component of affective empathy (i.e. mCC) might predominate during emotional involvement, and facilitate immersive experience.

This is obviously a post-hoc explanation, one that's hard to judge in the absence of actual exemplars of the experimental stimuli. Although the results were a bit underwhelming, I was happy the authors did not venture out on a rickety and hyperbolic limb, as the NYT did (gasp!) in Can ‘Neuro Lit Crit’ Save the Humanities? and Next Big Thing in English.

Footnotes

1 The Fearful and Neutral passages were matched for many factors that can affect reading:

...numbers of letters, words, sentences and subordinate sentence per passage, the number of persons or characters (as the narrative element), the type of intercharacter interaction and the incidence of supranatural events (i.e. magic) involved in text passages across the emotional categories.

Ron looked nervously at Harry. Harry betrayed nothing. You can be a wizard, Ron remembered, and you can be a man; it is good to be both, if you can, but if you must choose, it is better to be a man and not a wizard than a wizard and not a man.

Monday, October 06, 2014

Two Croatian academics with an anti-neuro ax to grind have written a cynical history of neuroword usage through the ages (Mazur & Rinčić, 2013). Actually, I believe the authors were being deliberately sarcastic (at times), since the article is rather amusing.1

Placing that phenomenon of "neuroization" of all fields of human thought and practice into a context of mostly unjustified and certainly too high – almost millenarianistic – expectations of the science of the brain and mind at the end of the 20th century, the present paper tries to analyze when the use of the prefix neuro- is adequate and when it is dubious.

Ključne riječi [keywords]:
brain; neuroscience; word coinage

Amir Muzur and Iva Rinčić are both on the Faculty of Medicine at the University of Rijeka, in the Department of Humanities and Social Sciences in Medicine. Their interests include the history of bioethics, bioethics and sociology, the history of medicine, and neuroscience.

Let aside the fact that a new decade did not begin in 1990 but a year later, with such pathos, George Bush Senior started an unprecedented avalanche of expectations, pompousness, and grants which will be lasting up today. The motives of launching the "Decade of the brain" were inspired by increasing awareness and fear of the treath [sic] of Alzheimer’s disease and neural sequels of drugs and AIDs, more than by the declared fascination by brain function.

Neurocriticism

The authors did intend to seriously critique the excesses of “neuroization” (since the title of the paper includes the word “Neurocriticism” after all), although it can be tricky to determine exactly when they're going over the top:

Scientists researching the brain cherish the idea that their work is extremely important, unique, and indispensable. They often venture into other fields and sciences without feeling any inferiority complex, convinced that their knowledge on human brain be sufficient to understand and interprete [sic] everything. ... Modern neuroscientists are like ancient alchemists, believing they are up to discover the most important secrets of the life elixir and the philosophers’ stone. Is not the hyperproduction of new names for (psudo)disciplines [sic] also a result of that arrogance?

A short primer of neuro-disciplines

Mazur and Rinčić (2013) then present their history of neurowords from 1681 to 2006, focusing on those that have become legitimate (or pseudo-legitimate) fields of study, some of which they characterize as “awkward caricatures” (e.g., neuroeconomics and neuromarketing).3

In the same year, it seems that two more new neuro-terms were coined: neuroethics, meaned [sic] for the neuroscience of ethics and the ethics of neuroscience (four years later, in May 2006, a Neuroethics society came to be at a conference in Asilomar in California), and neuroesthetics, as the study of the neural bases for the contemplation and creation of a work of art.

Neuroeconomics studies the neural underpinnings of making decisions, taking risks, and evaluating rewards. Probably the first to formulate the name was Paul Glimcher in 2003.4

The article confirms that the recent fad for “neuroization” is not justified. And not surprisingly, it ends on a pessimistically snarky (and utterly hyperbolic) note, putting all neuroscientists in their place:

In fact, nothing crucial has been discovered in neuroscience for quite a while, and the premordial entrapment in the mind-body problem still lasts: why, then, that explosion of "interest" in the brain at the end of the 20th and at the beginning of the 21st centuries? Is not it a contemporary variation of a historical periodical millenaristic movement, invoking a panacea for a society in general crisis? Neuro- seems to provide not only a desperate ultimate attempt at being original in science where everything has been said and done, but, morover [sic], a guaranty of attracting attention and simulating importance.

Amir Muzur, Iva Rinčić. Neurocriticism: a contribution to the study of the etiology, phenomenology, and ethics of the use and abuse of the prefix neuro-. JAHR – European Journal of Bioethics, Vol.4 No.7 Svibanj 2013. pp. 545-555.

Wednesday, October 01, 2014

September 30 is the last day of the fiscal year for the US government. So it's no coincidence that President Obama's BRAIN Initiative1 ended the year with a bang. The NIH BRAIN Awards were announced on the last possible day of FY2014, coinciding with the White House BRAIN Conference. A total of $46 million was dispersed among 58 awards involving over 100 scientists.

I watched most of the conference live stream. The entire video is now available for viewing on YouTube (and conveniently embedded at the bottom of this post). Below are a few idiosyncratic highlights.

I missed the early announcements (e.g., that the correct hashtag was #WHBRAIN) and introduction of the first speaker, a female graduate student. Next was John Holdren, senior advisor to the President on science and technology issues. My notes from his talk consisted of a series of buzz words and phrases, befitting a politician:

The first year budget is $100 million, with another $300 million allocated so far. A recurrent theme was the need for a sustained commitment to funding. Holdren (and others) mentioned the 12 year strategy for NIH, BRAIN 2025, which focuses on technologies, cells, and circuits.

The disconnect with reality came when he mentioned the burden of brain disorders and the prospect of curing them:

“Imagine if no family had to grapple with the helplessness and heartache of watching of a loved with Parkinson's or traumatic brain injury. Imagine if Alzheimer's or ALS or chronic depression were eradicated in our lifetimes.” [NOTE: Holdren is 70]

Ultimately we'd all like to eradicate these diseases, but that's not going to happen by 2025. Is it a good idea to mislead the public about the immediate clinical treatments arising from the NIH BRAIN Awards? How do we educate the public about the importance of basic science and technology development? DARPA is taking a different approach with their fast-tracking of deep brain stimulation treatments in humans. Their goals are even more ambitious: over a 5 year period, conduct clinical trials in human patients with 7 specified psychiatric and neurological disorders, some of which have never been treated with DBS.

Moving right along to the first panel, Cori Bargmann and Mark Schnitzer both did a fine job of discussing advances in circuits/networks and engineering/technology (see Storify below). The next panelists were clinician/researchers Geoffrey Manley on traumatic brain injury and Kerry Ressler on post-traumatic stress disorder. Ressler was bullish on new PTSD therapies, suggesting that it might be the most tractable psychiatric disorder. Manley, on the other hand, had a sobering assessment of TBI treatments derived from cellular neurobiology, noting that the field is on its 32nd or 33rd failed clinical trial.2

This is probably not what the White House wanted to hear, particularly since this panel was brought on to slyly connect the NIH BRAIN Awards to clinical disorders. But this is exactly what people need to hear to understand the utter complexity of trying to cure brain disorders, or at least treat them more effectively.

2The failure of a very promising clinical trial of progesterone for TBI was very recently announced ("based on 17 years of work with 200 positive papers in pre-clinical models"), although I couldn't find it. Here's the listing in ClinicalTrials.gov.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.